Diabetes mellitus has been associated with increased susceptibility to and greater severity of infections. Whether the pathophysiological changes associated with clinical diabetes and/or the genetic predisposition to diabetes lead to an impairment in the host immune response remains unclear. This proposal aims to determine the status of the immune response in the host with spontaneous diabetes and genetic predisposition to diabetes. The diabetic mutant mouse C57BL/Ks db/db during its prediabetic and overt diabetic state will be employed as the experimental animal model. The normal heterozygote C57BL/Ks db/plus and the wild strain without the diabetes mutation will serve as controls. Diabetes is also associated with hyperlipemia which independently may suppress the host immune response. Experiments to determine whether hyperlipemia has a role in the impaired response of the diabetic and prediabetic host will be carried out. An association between diabetes and the human group B coxsackieviruses has been demonstrated; a specific deficiency in the immune response of the host to these agents has been proposed. Experiments challenging the diabetic and genetically predisposed diabetic host with group B coxsackievirus will be conducted to determine whether such infection will unmask any specific immunological impairment(s).